Is MFAP5 p.Ser19= (c.57T>C) pathogenic?

MFAP5 p.Ser19= (c.57T>C) is classified Conflicting classifications of pathogenicity in MFAP5 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-01-28). Very rare (popmax 8.48e-05%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with MFAP5 p.Ser19= (c.57T>C)?

MFAP5 p.Ser19= (c.57T>C) is associated with Cardiovascular phenotype (ClinVar).

How common is MFAP5 p.Ser19= (c.57T>C) in the general population?

MFAP5 p.Ser19= (c.57T>C) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

MFAP5 p.Ser19=

c.57T>C · rs2136485750 · VCV1375380

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.031	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.1	GERP -3.7
Overall
CADD	7.064	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,836 alleles

Overall 6.2e-05% 1/1,613,706 alleles · very rare exomes 1/1,461,386 · genomes 0/152,320 · joint denominator

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: MFAP5
Protein: p.Ser19=
Coding: c.57T>C
MANE Select: NM_003480
dbSNP: rs2136485750
Type: single nucleotide variant
Location: chr12:8662048 (GRCh38)
Gene constraint: LOEUF 0.975 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.79

Full MFAP5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MFAP5 c.140-3C>A Uncertain significance ★★ same condition
MFAP5 c.335+4A>G Uncertain significance ★★ same condition
MFAP5 c.336-3C>T Uncertain significance ★★ same condition
MFAP5 p.Arg115His Uncertain significance ★★ same condition
MFAP5 p.Arg126His Uncertain significance ★★ same condition
MFAP5 p.Arg30Gln Uncertain significance ★★ ⚠ same condition
MFAP5 p.Arg93Ser Uncertain significance ★★ ⚠ same condition
MFAP5 p.Arg99Trp Uncertain significance ★★ ⚠ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/mfap5-p-ser19 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown